A trial to determine how several medications work individually and in combination to influence the feelings of cigarette smokers when smoking and when not smoking. It has been suggested that the combined drug administration, one causing a reaction, and one reducing activity, provides greater therapeutic benefit than the administration of one drug alone. There is support that nicotine and mecamylamine in combination provide reduced subjective effects of smoking, reduced side effects, and improved therapeutic efficiency as compared to either medication alone. Mecamylamine does not interfere with the reduction of cravings associated with the nicotine patch. So far, these findings are based on limited combinations of drugs and small sample sizes. This study uses a wide range of doses of both types of medications. The study will involve 35 male and female subjects, 18-50 years old. The goal is to have 27 subjects complete the protocol. All subjects must be current smokers of 20 cigarettes or more a day for at least two years, and must pass a standard physical examination including an electrocardiogram (tracing of the heart) and a urinalysis. Individuals with health or psychiatric problems will be excluded. Subjects will participate in nine, six hour sessions which shall be separated by one full day. At each session, the subjects will receive patches to be worn on the arm or the back, and will be given one of five medications to be swallowed. The patch or capsules may be placebos. At the beginning of each session, a thin needle for drawing blood will be inserted into the arm and will remain there throughout the entire session. Subjects will be asked to smoke at various times during the sessions, and will be asked to refrain from smoking for two or three hours at a time. Data collection on heart rate, blood pressure, and temperature will be done. Subjects will be asked to describe the nature of their experiences by answering questions and will be asked to perform various computerized tasks to help determine how the medications are effecting them.